Our long-term goal is to understand better allosteric effects in hemoglobins. Specifically we wish to interpret certain thermodynamic parameters of these phenomena in terms of structural origins and physiological implications. Our experimental approach is to obtain accurate thermodynamic data on selected hemoglobin materials by calorimetric and other direct methods. We propose to determine the overall standard free energy, enthalpy, entropy, and heat capacity changes for ligand reactions with various hemoglobins. Normal hemoglobins, Hb A and Hb F, would be compared to chemically modified forms of reduced cooperativity and to non-cooperative species (alpha, alpha beta, and beta 4) involving hemoglobin subunits. Hb S gelation would be studied to investigate how protein-protein aggregation affects the thermodynamics of ligand binding. Finally, trout hemoglobin I would be investigated as possibly a new type of genetic adaptation to a low temperature environment.